Role of Intermediate Filaments in Vesicular Traffic

Margiotta, Azzurra; Bucci, Cecilia

doi:10.3390/cells5020020

Cited by 54 publications

(47 citation statements)

References 188 publications

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“…Importantly, the small GTPase Rab7a regulates the assembly of vimentin affecting also its phosphorylation state [17,18,74]. Interestingly, in migrating cells, Rab7a-positive vesicles localize in the perinuclear region facing the wound while vimentin filaments are reorganized and reoriented in the direction of the wound (Fig.…”

Section: Discussionmentioning

confidence: 95%

Rab7a regulates cell migration through Rac1 and vimentin

Margiotta

Progida

Bakke

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Rab7a, a small GTPase of the Rab family, is localized to late endosomes and controls late endocytic trafficking. The discovery of several Rab7a interacting proteins revealed that Rab7a function is closely connected to cytoskeletal elements. Indeed, Rab7a recruits on vesicles RILP and FYCO that are responsible for the movement of Rab7a-positive vesicles and/or organelles on microtubule tracks, but also directly interacts with Rac1, a fundamental regulator of actin cytoskeleton, and with peripherin and vimentin, two intermediate filament proteins. Considering all these interactions and, in particular, the fact that Rac1 and vimentin are key factors for cellular motility, we investigated a possible role of Rab7a in cell migration. We show here that Rab7a is needed for cell migration as Rab7a depletion causes slower migration of NCI H1299 cells affecting cell velocity and directness.Rab7a depletion negatively affects adhesion and spreading onto fibronectin substrates, altering β1-integrin activation, localization and intracellular trafficking, and myosin X localization. In fact, Rab7a-depleted cells show 40% less filopodia and active integrin accumulates at the leading edge of migrating cells. Furthermore, Rab7a depletion decreases the amount of active Rac1 but not its abundance and reduces the number of cells with vimentin filaments facing the wound, indicating that Rab7a has a role in the orientation of vimentin filaments during migration. In conclusion, our results demonstrate a key role of Rab7a in the regulation of different aspects of cell migration.

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Section: Discussionmentioning

confidence: 95%

Rab7a regulates cell migration through Rac1 and vimentin

Margiotta

Progida

Bakke

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…Clathrinmediated endocytosis (CME) of Dll depends on Epsin 1 and 2, together with the alternative adaptor protein clathrin assembly lymphoid myeloid leukemia protein (CALM), rather than AP2, which is central to CME of most proteins (42). Vimentin interacts with the AP adaptor complexes to regulate endocytosis (18,72) and therefore might not affect Dll signaling. The view that vimentin potentiates Jagged function is corroborated by the data showing that Jagged expression correlates with vimentin expression in several tissues and in cancer, in particular.…”

Section: Discussionmentioning

confidence: 99%

Selective regulation of Notch ligands during angiogenesis is mediated by vimentin

Antfolk

Sjöqvist

Cheng

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Notch signaling is a key regulator of angiogenesis, in which sprouting is regulated by an equilibrium between inhibitory Dll4-Notch signaling and promoting Jagged-Notch signaling. Whereas Fringe proteins modify Notch receptors and strengthen their activation by Dll4 ligands, other mechanisms balancing Jagged and Dll4 signaling are yet to be described. The intermediate filament protein vimentin, which has been previously shown to affect vascular integrity and regenerative signaling, is here shown to regulate ligand-specific Notch signaling. Vimentin interacts with Jagged, impedes basal recycling endocytosis of ligands, but is required for efficient receptor ligand transendocytosis and Notch activation upon receptor binding. Analyses of Notch signal activation by using chimeric ligands with swapped intracellular domains (ICDs), demonstrated that the Jagged ICD binds to vimentin and contributes to signaling strength. Vimentin also suppresses expression of Fringe proteins, whereas depletion of vimentin enhances Fringe levels to promote Dll4 signaling. In line with these data, the vasculature in vimentin knockout (VimKO) embryos and placental tissue is underdeveloped with reduced branching. Disrupted angiogenesis in aortic rings from VimKO mice and in endothelial 3D sprouting assays can be rescued by reactivating Notch signaling by recombinant Jagged ligands. Taken together, we reveal a function of vimentin and demonstrate that vimentin regulates Notch ligand signaling activities during angiogenesis.

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“…Indeed, several types of organelles, such as nucleus, mitochondria, the Golgi apparatus, endosomes and lysosomes, interact with IFs [ 185 , 186 ]. Furthermore, a number of IFs proteins interact with vesicular trafficking regulatory proteins [ 187 ]. For instance, vimentin and peripherin bind to complex adaptor protein AP3 that is involved in transport between endosomes and lysosomes and their distribution and positioning are altered as consequence of changes in the IF network with consequent dysfunctions [ 188 ].…”

Section: Rab7 and The Cytoskeletonmentioning

confidence: 99%

Multiple Roles of the Small GTPase Rab7

Guerra

Bucci

2016

Cells

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326

309

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Rab7 is a small GTPase that belongs to the Rab family and controls transport to late endocytic compartments such as late endosomes and lysosomes. The mechanism of action of Rab7 in the late endocytic pathway has been extensively studied. Rab7 is fundamental for lysosomal biogenesis, positioning and functions, and for trafficking and degradation of several signaling receptors, thus also having implications on signal transduction. Several Rab7 interacting proteins have being identified leading to the discovery of a number of different important functions, beside its established role in endocytosis. Furthermore, Rab7 has specific functions in neurons. This review highlights and discusses the role and the importance of Rab7 on different cellular pathways and processes.

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Role of Intermediate Filaments in Vesicular Traffic

Cited by 54 publications

References 188 publications

Rab7a regulates cell migration through Rac1 and vimentin

Rab7a regulates cell migration through Rac1 and vimentin

Selective regulation of Notch ligands during angiogenesis is mediated by vimentin

Multiple Roles of the Small GTPase Rab7

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